Michael Rowbotham, a clinical neurologist and clinical neuroscientist specializing in chronic pain, has an international reputation as a leader in patient-oriented research on neuropathic pain mechanisms and clinical analgesic trials. The UCSF Pain Clinical Research Center (PCRC), started by Dr. Rowbotham in 1990, is a clinical research unit located in University-owned space that receives NIH, private, and industry support for exploratory clinical research and clinical trials. As a PI in the NINDS Program Project on Pain Mechanisms at UCSF, clinical research that translates advances from the Program's four basic science labs is fostered. Dr. Rowbotham has mentored 15 beginning clinical scientists from diverse backgrounds in the PCRC, and is developing a unique two year research/clinical training program that brings together the PCRC, the Neurology Pain Research Training Grant, and the Anesthesia-Pain Management Center Fellowship. K-24 support for a 5 year period will assist Dr. Rowbotham achieve his long-term career goal of establishing an integrated clinical research program that: (1) has a comprehensive pain research training curriculum for beginning clinical investigators; (2) conducts exploratory clinical research on pain mechanisms underlying different neuropathic pain disorders; (3) uses experimental pain models to evaluate new analgesics in healthy volunteers and patients, (4) translates basic science advances into well designed clinical trials to advance pain therapy; (5) relates pain mechanisms to opioid sensitivity, tolerance, and long term efficacy. The experiments in Project I will: (a) determine if opioid-insensitive chronic pains exist by simultaneously measuring the response of experimentally induced pain and ongoing clinical pain to i.v. remifentanil infusion; (b) determine if a prolonged i.v. remifentanil infusion can produce acute analgesic tolerance to both the experimentally induced pain and hyperalgesia and the ongoing chronic pain; and (c) prospectively assess development of opioid analgesic tolerance during long term oral opioid therapy. Project II will test the hypothesis that development of chronic post-herpetic neuralgia after herpes zoster strongly depends on the severity of the initial neural injury and the quality of neural recovery. Patients with acute zoster pain will be followed for 6 months on measures of pain intensity, mood, quality of life, allodynia, extent of affected skin, quantitative tests of sensory function, response to controlled applications of capsaicin, and serial skin punch biopsy measurement of cutaneous innervation in affected and normal skin.